The principal goal of the studies proposed in this application is to identify and to characterize the biosynthetic steps and molecular species involved in the production of the putative peptide neurotransmitter substance P using the basal ganglia as a model. I have recently observed biosynthesis and transport of radiolabeled substance P in the striatonigralprojection in individual free-running rats. These studies will be continued in order to examine the dynamics of the in vivo biosynthesis and transport of striatonigral substance P and its regulation by using an in vivo amino acid labeling paradigm and peptide chemistry methods. A substance P precursor protein will be isolated in these experiments using immunological and protein chemistry methods. These studies will be extended to the identification of a striatal messenger RNA molecule coding for the substance P precursor protein by using specific nucleic acid hybridization techniques with syntyhetic oligonucleotide probes. The primary protein translation product will be studied by using striatal mRNA and cell-free translation, immunoprecipitation and protein chemistry methods. These studies will provide a better understanding of basal ganglia substance P peptidergic neurons and their reported relationship to the neurodegenerative diseases Parkinsonism and Huntington's chorea.